Arseic (As) carcinogenesis is a unique example of discrepancy between positive human findings and negative animal tests. Two hypotheses are investigated to clear this discrepancy: (a) speciesspecific differences of As metabolism between humans and laboratory rodents used in carcinogenesis tests; (b) requirements for combined exposures with other agents in a cocarcinogenic interaction. Prelimiary findings show that the hamster is able to methylate inorganic arsenic in vivo. This biotransformation is similar to that in humans and considerably more effective than in the rat, supporting the selection of the hamster as a more appropriate species for metabolic studies and carcinogenesis tests. Carinogenesis studies are planned on combinations of As with other compounds. Because of the complexity of these studies in vivo, epithelial culture models are selected in which to investigate arsenic metabolism and its interaction with other compounds. Conditions needed for arsenic methylation and the effect of arsenic on epidermal cell differentiation and keratin synthesis in culture are studied. Primary mouse epidermal cell cultures are used and primary hamster epidermal cell and bronchial epithelial cell culture systems are considered for future use. In vivo carcinogenesis protocols will be developed according to the information obtained from in vivo and in vitro metabolic studies.